Molecular cloning and functional expression of the K+ channel KV7.1 and the regulatory subunit KCNE1 from equine myocardium

Abstract

Background: The voltage-gated K⁺-channel K_V7.1 and the subunit KCNE1, encoded by the KCNQ1 and KCNE1 genes, respectively, are responsible for termination of the cardiac action potential. In humans, mutations in these genes can predispose patients to arrhythmias and sudden cardiac death (SCD).

Aim: To characterize equine K_V7.1/KCNE1 currents and compare them to human K_V7.1/KCNE1 currents to determine whether K_V7.1/KCNE1 plays a similar role in equine and human hearts.

Methods: mRNA encoding K_V7.1 and KCNE1 was isolated from equine hearts, sequenced, and cloned into expression vectors. The channel subunits were heterologously expressed in Xenopus laevis oocytes or CHO-K1 cells and characterized using voltage-clamp techniques.

Results: Equine K_V7.1/KCNE1 expressed in CHO-K1 cells exhibited electrophysiological properties that are overall similar to the human orthologs; however, a slower deactivation was found which could result in more open channels at fast rates.

Conclusion: The results suggest that the equine K_V7.1/KCNE1 channel may be important for cardiac repolarization and this could indicate that horses are susceptible to SCD caused by mutations in KCNQ1 and KCNE1.

Keywords: Cardiac electrophysiology; Equine; Horse; K(V)7.1; KCNE1; KCNQ1.